1-(2-氯乙基)四氢-1H,5H-[1,3,2]二氮杂磷酰基[2,1-b][1,3,2]氧杂氮杂磷杂苯9-氧化物 | 64724-10-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 中文名称: 1-(2-氯乙基)四氢-1H,5H-[1,3,2]二氮杂磷酰基[2,1-b][1,3,2]氧杂氮杂磷杂苯9-氧化物
• 英文名称: 1-(2-chloro-ethyl)-tetrahydro-[1,3,2]diazaphospholo[2,1-b][1,3,2]oxazaphosphinine 9-oxide
• 英文别名: 1-(2-chloro-ethyl)-tetrahydro-[1,3,2]diazaphospholo[2,1-b][1,3,2]oxazaphosphinine (S)-9-oxide；1,7-diaza-7-(2-chloro-ethyl)-5-oxa-6-phospha-bicyclo(4.3.0)nonan-6-one；1-(2-Chloroethyl)tetrahydro-1H,5H-[1,3,2]diazaphospholo[2,1-b][1,3,2]oxazaphosphorine 9-oxide；9-(2-chloroethyl)-2-oxa-6,9-diaza-1λ5-phosphabicyclo[4.3.0]nonane 1-oxide
• CAS: 64724-10-3
• 化学式: C₇H₁₄ClN₂O₂P
• 分子量: 224.627
• InChiKey: PWGJOPOXRGOWLB-UHFFFAOYSA-N

物化性质

• 熔点：
  134-138°C
• 溶解度：
  溶于甲醇、水

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2-氯乙基)四氢-1H,5H-[1,3,2]二氮杂磷酰基[2,1-b][1,3,2]氧杂氮杂磷杂苯9-氧化物 在 水 作用下， 以72%的产率得到3-(2-氯乙基)八氢-2-羟基-1,3,6,2-氧杂二氮杂磷杂八环 2-氧化物
  参考文献：
  名称：

  Chemical and Biological Evaluation of Hydrolysis Products of Cyclophosphamide

  摘要：

  P-31 NMR spectroscopy was used to study the products of the decomposition of cyclophosphamide (1) in buffered solutions at pH's ranging between 1.2 and 8.6 at 20 degrees C and at pH 7.4 at 37 degrees C. At pH 1.2, 1 undergoes a rapid breakdown (t(1/2) = 1.4 days) of the two P-N bonds, giving compounds 2 [HN(CH2CH2Cl)(2)] and 3 [H2N(CH2)(3)OP(O)(OH)(2)] as hydrochlorides. No intermediates were detected. At pH's between 5.4 and 8.6, hydrolysis of 1 during 17 days leads to the sole and previously unknown nine-membered ring compound 13. 13 results from the intramolecular alkylation of 1 giving the bicyclic compound 7 followed by the exothermal hydrolytic breakdown of the P-N bond of its six-membered ring. At pH 2.2 and 3.4, the two hydrolytic pathways coexist since, beside compounds 2 and 3, the hydrochloride of compound 9 [Cl(CH2)(2)NH(CH2)(2)NH(CH2)(3)OP(O)(OH)(2)] is formed, resulting from the acid-catalyzed breakdown of the P-N bond in the nine-membered ring compound 13. At pH 2.2, the presence of chloride ion affected neither the stability of 1 nor the contribution of the two competing hydrolytic pathways. At pH's ranging from 3.4 to 8.6, there is little degradation of 1 since more than 95% of initial 1 was still present after 7 days at 20 degrees C. Under physiological conditions (pH 7.4, 37 degrees C) after 6 days, 45% of 1 is hydrolyzed (t(1/2) = 6.6 days), leading essentially (30% of initial 1) to the nine-membered ring compound 13. The rate of hydrolysis of 13 and the nature of its hydrolysis products were found to depend on pH over the range 0-8.6. After a single ip injection to mice, compounds 3, 9, and 13 were less toxic than 1. They did not exhibit any direct cytotoxic efficacy on the colony-forming capacity of L1210 cells in vitro, and they had no antitumor activity in vivo against P388 leukemia.

  DOI：

  10.1021/jm00049a018
• 作为产物：
  描述：

  环磷酰胺 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 生成 1-(2-氯乙基)四氢-1H,5H-[1,3,2]二氮杂磷酰基[2,1-b][1,3,2]氧杂氮杂磷杂苯9-氧化物
  参考文献：
  名称：

  环磷酰胺合成和结构研究的降解产物

  摘要：

  摘要 环磷酰胺在中性或微酸性水溶液中的降解开始于分子内烷基化，导致中间双环化合物立即水解为九元杂环。随后酸催化的 PN 键水解产生磷酸单酯。在强酸性溶液 (1 N HCl) 中，环磷酰胺仅分解为双 (2-氯乙基)-胺和相应的磷酸单酯 H2N(CH2)3OP(O)(OH)2。在加热到熔点的环磷酰胺固体样品中，第一种途径比第二种途径占优势。磷化合物的结构通过 1H 和 31P NMR 光谱和合成确定。

  DOI：

  10.1080/10426509608545193

文献信息

• Synthesis and absolute configuration assignments of enantiomeric forms of ifosphamide, sulfosphamide, and trofosphamide
  作者：K. Pankiewicz、R. Kinas、W. J. Stec、A. B. Foster、M. Jarman、Jan M. S. Van Maanen

  DOI：10.1021/ja00520a015

  日期：1979.12
• High-resolution nuclear magnetic resonance investigations of the chemical stability of cyclophosphamide and related phosphoramidic compounds
  作者：Gerald Zon、Susan Marie Ludeman、William Egan

  DOI：10.1021/ja00459a041

  日期：1977.8
• Gilard Veronique, Martino Robert, Malet-Martino Marie-C., Kutscher Bernha+, J. Med. Chem, 37 (1994) N 23, S 3986-3993
  作者：Gilard Veronique, Martino Robert, Malet-Martino Marie-C., Kutscher Bernha+

  DOI：——

  日期：——
• BRUIJN, E. A. DE;OOSTEROM, A. T. VAN;LECLERCQ, P. A.;HAAN, J. W. DE;VEN, +, BIOMED. AND ENVIRON. MASS SPECTROM., 14,(1987) N 11, 643-647
  作者：BRUIJN, E. A. DE、OOSTEROM, A. T. VAN、LECLERCQ, P. A.、HAAN, J. W. DE、VEN, +

  DOI：——

  日期：——
• FORMULATIONS OF CYCLOPHOSPHAMIDE LIQUID CONCENTRATE
  申请人：AuroMedics Pharma LLC

  公开号：US20150320774A1

  公开（公告）日：2015-11-12

  Cyclophosphamide containing compositions preferably in the form of solutions having extended stability are disclosed. The compositions contain cyclophosphamide, ethanol and an ethanol soluble acidifying agent such as citric acid. Ready to dilute or ready to use cyclophosphamide containing composition of the invention maintain high levels cyclophosphamide content after about 18 or 24 months at a temperature of about 5° C.